When a living body is exposed to various stresses such as exposure to environmentally harmful substances including ultraviolet ray or fine particle and inflammation caused by viral or bacterial infection, active oxygen species are produced in the cells and protein and gene are oxidized and disordered. Therefore, a living body has a system where redox response is basically a defensive mechanism against active oxygen species and one of the representative examples thereof is a thioredoxin system.
Thioredoxin has been found as a coenzyme which donates hydrogen ion to ribonucleotide reductase which is an essential enzyme for the DNA synthesis of Escherichia coli. Thioredoxin has an active site of -Cys-Gly-Pro-Cys- and is an intracellular oxidation-reduction controlling factor wherein a reduction type which forms dithiol (—SH—SH) and an oxidation type which forms a disulfide (S—S) bond between two cysteine residues are present.
It has been made clear already that thioredoxin is induced by ultraviolet ray, radioactive ray, oxidizing agent, infection of virus, ischemic reperfusion injury and administration of anticancer agent. It has been reported that thioredoxin induced by various stresses extinguishes singlet oxygen or hydroxyl radical solely and also acts in living body as an antioxidant which extinguishes active oxygen species by a cooperative action with peroxyredoxin whereby thioredoxin controls activity of transcription factor adjusting various gene expressions and signal transmitting molecules in cells. Accordingly, it is expected that, when thioredoxin is induced, then cells, tissues, organs, etc. are able to be protected from a morbid state on the basis of various oxidation-reduction phenomena caused in the cells or a previous stage thereof. And, therefore, studies for substances inducing thioredoxin have been developed already and, for example, there is a disclosure for isoprenoid compounds as an inducing substance (refer to the Patent Document 1).
As one of the diseases and morbid states caused by imbalance of the above-mentioned oxidation/antioxidant or redox state, there is a lung disease including chronic obstructive pulmonary disease (COPD), etc. COPD is a disease where a morbid state is a persistently clogged state of airway caused by sticking of sputum in one's throat, swelling of bronchus (chronic bronchitis) and destruction of pulmonary alveoli (pulmonary emphysema) as a result of chronic inflammation in airway or peripheral lung tissues by inhalation of toxic fine particles and its biggest cause is smoking. In cigarette smoke, a lot of oxidant is contained and the lung is in a state of being exposed to oxidation stress. Accordingly, thioredoxin which has been known to have anti-inflammatory and cytoprotective actions is suggested to suppress the tissue injury and inflammation by smoking. In fact, it has been reported that, in healthy smokers, concentration of thioredoxin in blood is significantly high as compared with nonsmokers and it is likely that an increase in production of thioredoxin acts as a protective mechanism against chronic smoking which is a persistent oxidation stress. From such a viewpoint, it is appropriate to use thioredoxin as a therapeutic strategy and it has been disclosed already that thioredoxin is effective as a preventive or treating agent for chronic obstructive pulmonary diseases (refer to the Patent Document 2).
Disclosed pharmacological activity regarding extracts from inflamed tissues inoculated with vaccinia virus includes the following: analgesic, sedative, anti-stress and anti-allergic actions (refer to the Patent Document 3); immune stimulation, anticancer and cirrhosis inhibition actions (refer to the Patent Document 4); a therapeutic effect for idiopathic thrombocytopenic purpura (refer to the Patent Document 5); therapeutic effects for post-herpetic neuralgia, cerebral edema, dementia, spinocerebellar degeneration and the like (refer to the Patent Document 6); therapeutic effects for Raynaud's disease, diabetic neuropathy, sequelae of subacute myelo-optic neuropathy and the like (refer to the Patent Document 7); kallikrein production inhibition and peripheral circulatory disturbance amelioration actions (refer to the Patent Document 8); bone atrophy amelioration action (refer to the Patent Document 9); nitric oxide production inhibition action effective in the treatment of septicemia and endotoxin shock (refer to the Patent Document 10); a curative effect for osteoporosis (refer to the Patent Document 11); a curative effect for AIDS based upon inhibition actions for Nef action and chemokine production (refer to the Patent Documents 12 and 13); a therapeutic effect for ischemic diseases such as cerebral infarctions (refer to the Patent Document 14); therapeutic effect for fibromyalgia (refer to the Patent Document 15); therapeutic effect for infectious diseases (refer to the Patent Document 16) and the like.    The Patent Document 1: Japanese Patent Laid-Open Publication No. 2001-322929    The Patent Document 2: Japanese Patent Laid-Open Publication No. 2005-60408    The Patent Document 3: Japanese Patent Laid-Open Publication No. S53-101515    The Patent Document 4: Japanese Patent Laid-Open Publication No. S55-87724 (pages 3, 5 and 6 in particular)    The Patent Document 5: Japanese Patent Laid-Open Publication No. H01-265028 (pages 1 and 2 in particular)    The Patent Document 6: Japanese Patent Laid-Open Publication No. H01-319422 (pages 3 and 4 in particular)    The Patent Document 7: Japanese Patent Laid-Open Publication No. H02-28119 (page 3 in particular)    The Patent Document 8: Japanese Patent Laid-Open Publication No. H07-97336 (page 4 in particular)    The Patent Document 9: Japanese Patent Laid-Open Publication No. H08-291077    The Patent Document 10: Japanese Patent Laid-Open Publication No. H10-194978    The Patent Document 11: Japanese Patent Laid-Open Publication No. H11-80005 (pages 2 and 3 in particular)    The Patent Document 12: Japanese Patent Laid-Open Publication No. H11-139977    The Patent Document 13: Japanese Patent Laid-Open Publication No. 2000-336034 (pages 2 and 3 in particular)    The Patent Document 14: Japanese Patent Laid-Open Publication No. 2000-16942    The Patent Document 15: International Patent Publication WO 2004/039383    The Patent Document 16: Japanese Patent Laid-Open Publication No. 2004-300146